It is currently known that, depending on the type of disease to be diagnosed, there are cases where, if a healthy person is compared to an afflicted person, the content of a specified component in the blood will differ drastically. Thus, diagnosis of such diseases is performed by investigating the content of a specified component in the blood. Furthermore, with this sort of diagnostic method for diseases, it is necessary to analyze samples collected from numerous subjects. Thus, a screening test is performed as the primary test so as not to increase the work load.
Mass analysis methods, in which metabolites in blood are subjected to mass analysis, are considered to be important as screening tests. Devices using a mass analysis method include atmospheric pressure ionization mass analysis devices in which ions of sample molecules are generated under atmospheric pressure and the obtained ions are placed into a vacuum and analyzed. Furthermore, atmospheric pressure ionization mass analysis devices employ a flow injection method as the sample introduction method, whereby the sample solution is analyzed while being fed (for example, see Patent Literature 1). With the flow injection method, analysis is performed without performing separation of components by a column, thus allowing samples to be analyzed in a shorter time. Thus, it is employed for screening tests, where it is necessary to analyze a lot of samples. Furthermore, a mass analysis method is combined with other ionization method such as direct ionization by which ion is ionized with laser radiation or Direct Analysis in Real Time (DART) ionization by which ion is ionized with ionized gas. (for example, see non-Patent Literature 1)
FIG. 8 is a schematic diagram illustrating an example of an atmospheric pressure ionization mass analysis device employing a flow injection method. The atmospheric pressure ionization mass analysis device 101 comprises an MS 10 and a computer (control unit) 130. In MS 10, an ionization chamber 11, a first intermediate chamber 12 adjacent to the ionization chamber 11, a second intermediate chamber 13 adjacent to the first intermediate chamber 12, and a mass analysis chamber 14 adjacent to the second intermediate chamber 13 are consecutively arranged across partition walls. Inside the mass analysis chamber 14, there is provided a first mass analysis unit 16, a collision cell 26, a second mass analysis unit 17, and a detector 18. Furthermore, an inert gas such as argon gas is introduced into the collision cell 26.
In this sort of atmospheric pressure ionization mass analysis device 101, the sample solution and nitrogen gas (nebulizer gas) are sprayed into the ionization chamber 11 by a sprayer (probe) 15. FIG. 9 (a) is side view of the sprayer, and FIG. 9 (b) is an enlarged cross-sectional view of A shown in FIG. 9 (a).
Sprayer 15 has a double pipe structure, and the sample solution is sprayed out from the inside of round pipe 159. Furthermore, nitrogen gas is sprayed out from the space between round pipe 159 and round tubular nozzle 152. This arrangement causes the sprayed out sample solution to be atomized in the form of a mist due to the effect of collision with the nitrogen gas sprayed out around the round pipe 159. Furthermore, a wire (not illustrated) is connected to the tip of the nozzle 152 so as to apply a high voltage of several kV from a voltage source (not illustrated), whereby ionization is performed.
In this way, sample solution which successively flows out from the sprayer 15 becomes ionized. The ions generated as a result in the ionization chamber 11 are fed in sequence through solvent removal tube 19, first ion lens 21 inside first intermediate chamber 12, skimmer 22, octapole 23 and focus lens 24 inside second intermediate chamber 13, and input lens 25, into the mass analysis chamber 14. Ions which have been fed into the mass analysis chamber 14 are subjected to elimination of unneeded ions by means of the quadrupole inside the first mass analysis unit 16, ions are destroyed in collision cell 26, unneeded ions are further eliminated by means of the quadrupole inside second mass analysis unit 17, and only ions of a specified mass m/charge z which have reached the detector 18 are detected.
Here, only ions with m/z corresponding to the applied voltage selectively pass through the quadrupoles inside the first mass analysis unit 16 and the second mass analysis unit 17, to which a voltage is applied in which a direct current voltage and a high frequency voltage are superimposed, and thus, precursor ions which are to be allowed through the first mass analysis unit 16 and product ions which are to be allowed through the second mass analysis unit 17 are selected, and voltage is applied so that only ions with the selected m/z will pass through. Once the precursor ions and product ions corresponding to the component to be measured are selected, ions with the m/z corresponding to the product ions will pass through the first mass analysis unit 16 and be dissociated in the collision cell 26, and the corresponding product ions will pass through the second mass analysis unit 17 and arrive at the detector 18. The m/z of ions which pass through the quadrupole depends on the applied voltage, so by scanning the applied voltage, ion intensity signals for ions of multiple m/z ratios of interest are acquired in the detector 18. The information (ion intensity signal) acquired in the detector 18 is then outputted to a computer 130.
The computer 130 comprises a CPU 131, and is further connected to a memory 132, a keyboard 33a and mouse 33b, which are input devices, and a display device 34 comprising a monitor screen 34a and the like. In the detector 18, the sample is cleaved into individual ions, and the ion intensity is detected for each m/z. By repeating this measurement at short time intervals, multiple mass spectra are generated, with m/z on the horizontal axis and detected intensity on the vertical axis. Furthermore, focusing one's interest on the detected intensity of ions with a given m/z among the detected intensities of ions of multiple m/z ratios, by arranging the detected intensity of ions with the m/z of interest in the time axis direction, a mass chromatogram is generated. Moreover, by adding together mass chromatograms for multiple m/z ratios of interest, a total ion chromatogram is generated.
As a result, in the screening test, by computing the content of a specified component on the basis of peak area value and detected intensity value appearing on the mass chromatogram of a given m/z corresponding to the specified component, the tester, etc. finds samples in which the content of the specified component differs drastically from among a large number of samples.